Gliederung

Over the past 30 years the attention towards purines and pyrimidines as signalling molecules has grown constantly. Purinoceptors are divided into two families, i.e. P1-purinoceptors and P2-purinoceptors. P2-Purinoceptors are expressed in a large number of blood pressure regulating tissues. Vascular smooth muscle cells of arteries, endothelial cells of small peripheral vessels and glomeruli, and renal mesangial cells all involve P2-purinoceptors in their regulating mechanisms. The P2-purinergic-system could be therefore a relevant factor within the pathogenesis of hypertension and associated target organ damage. Several genetic rat models are established tools in experimental genetic studies particularly in hypertension research. Most of the P2-purinoceptor-loci have not been mapped in the rat. We therefore employed the rat-hamster radiation hybrid panel T55V3 to localize P2-purinoceptor-genes in the rat genome. We further investigated their genomic position with regard to known quantitative trait loci (QTL) for hypertensive disease phenotypes. We identified co-localizations of several loci with QTL linked to hypertension, cardiac hypertrophy, renal failure and stroke. We could also confirm the wide spread expression of P2-purinoceptors in heart and renal tissue by means of RT-PCR analysis. Our results support the potential involvement of P2-purinorecptors in hypertension and target organ damage. Our data provide the basis for further studies on the genetics of the P2-purinorecptors in hypertensive disease.